Glycosaminoglycans (GAGs)

Glycosaminoglycans (GAGs) are long, unbranched polysaccharides composed of repeating disaccharide units that are highly negatively charged due to the presence of sulfate and carboxyl groups. They are found in the extracellular matrix (ECM) and are critical for tissue hydration, elasticity, and cell signaling.

Structure:

  • Each repeating disaccharide unit typically consists of:
    • A hexuronic acid (e.g., glucuronic acid or iduronic acid)
    • An amino sugar (e.g., N-acetylglucosamine or N-acetylgalactosamine)
  • The chains are often sulfated (except for hyaluronic acid), which gives them a strong negative charge, allowing them to attract water and cations.

Key Functions:

FunctionDescription
HydrationAttract water to keep tissues moist and resilient
Structural supportProvide compressive strength in cartilage and skin
Cell signalingBind and regulate growth factors and cytokines
FiltrationHelp in kidney glomerulus and basement membrane filtration
Wound healingPromote cell migration and matrix formation

Major Types of GAGs:

GAG TypeKey FeaturesFound In
Hyaluronic acidNon-sulfated, very largeSynovial fluid, skin, vitreous humor
Chondroitin sulfateSulfated, provides resistance to compressionCartilage, tendons, ligaments
Dermatan sulfateFlexible and sulfatedSkin, blood vessels, heart valves
Heparan sulfateHighly sulfated, involved in signalingBasement membranes, cell surfaces
HeparinMost highly sulfated; anticoagulantMast cells (used medically as blood thinner)
Keratan sulfateSulfated, lacks uronic acidCornea, cartilage, intervertebral discs

GAGs and Proteoglycans:

  • Most GAGs are attached to core proteins to form proteoglycans (e.g., aggrecan in cartilage).
  • Hyaluronic acid is the only GAG that does not bind to a core protein, but it interacts non-covalently with proteoglycans to form large complexes.

Clinical Relevance:

  • Osteoarthritis: Loss of GAGs like chondroitin sulfate reduces cartilage resilience.
  • Mucopolysaccharidoses: Genetic disorders where GAGs accumulate due to enzyme deficiencies.
  • Cosmetic and medical uses: Hyaluronic acid is used in skin fillers and joint injections.
  • Anticoagulant therapy: Heparin is widely used to prevent blood clots.

Summary Table:

FeatureDescription
CompositionRepeating disaccharides (amino sugar + uronic acid)
ChargeHighly negative (due to sulfate and carboxyl groups)
FunctionHydration, support, signaling, filtration
Found InECM, cartilage, skin, basement membrane, joints
TypesHyaluronic acid, chondroitin sulfate, dermatan sulfate, etc.